The surprising antidepressant effects of sleep deprivation

By Alpana Mohta, MD, DNB, FEADV, FIADVL, IFAAD | Fact-checked by Barbara Bekiesz
Published January 18, 2024

Key Takeaways

  • While prolonged sleep deprivation's adverse effects are well-documented, the impacts of short-term sleep disruption are less understood.

  • Wake therapy involves intentional sleep deprivation for about 24 to 36 hours. In some individuals, this approach quickly reduces symptoms of depression.

  • The increased dopamine release and enhanced synaptic plasticity of this type of therapeutic intervention can result in a lasting antidepressant effect.

In the United States, major depressive episodes affect around 8% of the adult population, translating to about 21 million individuals experiencing depressive symptoms at any given time.[] Of these, nearly 14.5 million adults develop at least one episode of major depression with severe impairment every year. Despite this high prevalence, only 61% of patients with a major depressive episode receive treatment, and many require hospitalization. 

Conventional treatments like antidepressant medication, coupled with light therapy and exercise, are common, but they often take time to show results. This delay is critical, especially for patients in acute distress or with suicidal thoughts. 

Enter “wake therapy”—an innovative approach offering more immediate relief for those battling the intense effects of depression.

Therapeutic interventions for disordered sleep

Wake therapy, involving 24-36 hours of full or partial sleep deprivation, was first proposed as a treatment for depressive disorder in the 1950s.[] While initial studies showed promise, there were mixed results in the following decades due to methodological inconsistencies and varied response definitions.

Yet recent studies suggest that combining wake therapy with other treatments, such as light therapy and sleep-phase-advance therapy, might sustain its benefits. 

  • A 2017 randomized, controlled trial involved 64 hospitalized patients with moderate-to-severe depression. Those who received three wake therapy sessions in 1 week, along with 30 minutes of light treatment daily, had a significant decrease in depressive symptoms in the first week.[]

  • A similar study, following the same protocol, found a notable reduction in depressive symptoms within the first 6 days, with 41% of patients responding to the treatment and 19% achieving remission.[]

  • A 2023 study from PNAS showed that just one sleepless night rapidly improved the mental state in a subset of cases with depression. Following this wake therapy, brain scans revealed increased connections between two brain areas—the amygdala and the anterior cingulate cortex.[]

Insights from sleep-deprived mice

Wake therapy has been linked to improved mood in depression due to its impact on circadian rhythms, neuroendocrine hormone production, and brain activity. Recently, researchers from Northwestern University published a study in Neuron exploring the effects of sleep deprivation on depressive symptoms using mice.[] 

The mice, not predisposed to psychological problems, experienced mild sleep disruption akin to a human all-nighter. This led to manic behaviors like increased aggression, heightened activity, and excessive sexual behavior, contrasting with the calm behavior of well-rested control mice.

Key to this study was the focus on the brain's reward system, particularly dopamine, a neurotransmitter linked to pleasure and motivation. During sleep deprivation, there was a notable increase in dopamine activity in the medial prefrontal cortex. When dopamine activity in this area was inhibited, the antidepressant effects ceased, suggesting this as the key region for mood elevation and a potential focus for future therapies. 

Post-sleep deprivation, there was an observable increase in the formation of new neural connections in the mice's brains, indicating a rewiring to maintain heightened mood. However, disrupting these new connections negated the antidepressant effects.

According to an associated news article published on Northwestern's website, the study authors explained that “chronic sleep loss is well studied, and its uniformly detrimental effects are widely documented.”[] However, they continued, “brief sleep loss—like the equivalent of a student pulling an all-nighter before an exam—is less understood.” 

"We found that sleep loss induces a potent antidepressant effect and rewires the brain."

Authors, Neuron

“This is an important reminder of how casual activities, such as sleepless nights, can fundamentally alter the brain in a few hours,” they said, further explaining that this paradoxical effect of sleep deprivation could be our body’s response to “some sort of danger where you need a combination of relatively high function with an ability to delay sleep.”

Results shouldn’t be generalized

Often, there is a U-shaped correlation between the amount of sleep and the onset of depression, where both inadequate and excessive sleep significantly increases the likelihood of developing depressive disorder.[] 

The Neuron authors cautioned against using sleep deprivation as a mood booster, stressing the value of a good night’s sleep and suggesting healthier alternatives such as exercise. This research, they asserted, is more about tailoring antidepressant treatments rather than promoting sleep deprivation as a remedy.

What this means for you

We have all felt the paradox of feeling simultaneously exhausted and alert following a night without sleep. Wake therapy works by stimulating dopamine activity in the medial prefrontal cortex. While wake therapy could be beneficial for patients in controlled, short-term scenarios, it might not work for every patient—it is only a part of the broader treatment plan and should be supervised by a physician due to potential side effects and relief that is only temporary.

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